Department of Neurology and Clinical Neuroscience, Yamaguchi University Graduate School of Medicine, Ube, Japan.
J Neurol Neurosurg Psychiatry. 2012 Mar;83(3):288-97. doi: 10.1136/jnnp-2011-300434. Epub 2011 Nov 19.
In neuromyelitis optica (NMO), the destruction of the blood-brain barrier (BBB) has been considered to be the first step of the disease process. It is unclear whether sera from patients with NMO can open the BBB, and which component of patient sera is most important for this disruption.
The effects of sera from antiaquaporin4 (AQP4) antibody positive NMO patients, multiple sclerosis patients and control subjects were evaluated for expression of tight junction proteins and for transendothelial electrical resistance (TEER) of human brain microvascular endothelial cells (BMECs). Whether antibodies against human BMECs as well as anti-AQP4 antibodies exist in NMO sera was also examined using western blot analysis.
Expression of tight junction proteins and TEER in BMECs was significantly decreased after exposure to NMO sera. However, this effect was reversed after application of an antivascular endothelial growth factor (VEGF) neutralising antibody. Antibodies against BMECs other than anti-AQP4 antibodies were found in the sera of NMO patients whereas no specific bands were detected in the sera of healthy and neurological controls. These antibodies apparently disrupt the BBB by increasing the autocrine secretion of VEGF by BMECs themselves. Absorption of the anti-AQP4 antibody by AQP4 transfected astrocytes reduced AQP4 antibody titres but was not associated with a reduction in BBB disruption.
Sera from NMO patients reduce expression of tight junction proteins and disrupt the BBB. Autoantibodies against BMECs other than anti-AQP4 antibodies may disrupt the BBB through upregulation of VEGF in BMECs.
在视神经脊髓炎（NMO）中，血脑屏障（BBB）的破坏被认为是疾病过程的第一步。目前尚不清楚 NMO 患者的血清是否可以打开 BBB，以及患者血清中的哪个成分对此破坏最为重要。
评估抗水通道蛋白 4（AQP4）抗体阳性的 NMO 患者、多发性硬化症患者和对照者的血清对人脑血管内皮细胞（BMEC）紧密连接蛋白的表达和跨内皮电阻（TEER）的影响。还使用 Western blot 分析检查 NMO 血清中是否存在针对人 BMEC 的抗体以及抗 AQP4 抗体。
暴露于 NMO 血清后，BMEC 中紧密连接蛋白的表达和 TEER 明显降低。然而，在用血管内皮生长因子（VEGF）中和抗体处理后，这种作用被逆转。在 NMO 患者的血清中发现了针对除 AQP4 抗体以外的 BMEC 的抗体，而在健康和神经对照组的血清中则未检测到特异性条带。这些抗体显然通过增加 BMEC 自身的 VEGF 的自分泌而破坏 BBB。AQP4 转染星形胶质细胞对 AQP4 抗体的吸收降低了 AQP4 抗体滴度，但与 BBB 破坏的减少无关。
NMO 患者的血清降低了紧密连接蛋白的表达并破坏了 BBB。除抗 AQP4 抗体以外的针对 BMEC 的自身抗体可能通过上调 BMEC 中的 VEGF 来破坏 BBB。
